The overall objective of this NCRR Shared Instrument Grant application is to upgrade the current Department of Human Genetics Shared DNA Sequencing Core into an Institution-wide, state-of-the-art core for sequencing, genotyping, and loss of heterozygosity (LOH) analysis to facilitate and enhance the research efforts of all NIH-funded Investigators at the Mount Sinai School of Medicine. The specific request is for a High-Throughput DNA Sequencing/Gentoyping System for DNA sequencing and fragment analysis. The requested ABI 3700 is a proven, high-quality capillary-array sequencer that can support the high- throughput needs of the highly productive, NIH-supported research at Mount Sinai. This application is strengthened by the previous 5 years of experience of its Principal Investigator in providing high-quality DNA sequencing, genotyping and oligonucleotide synthesis primarily for the Faculty of the Department of Human Genetics using an ABI 377XL Automated DNA Sequencer, ABI Catalyst 877 robotic workstation, ABI 394 DNA synthesizer and Sun SPARC system server on our Institutional Ethernet backbone. With this grant and additional Institutional support, this well-functioning Core will be upgraded and enhanced to provide these services to all NIH-funded and other Investigators at Mount Sinai. The Core will provide in-house expertise and consultation services for all sequencing, genotyping, and LOH projects. This Core will meet the intense needs of investigators for on-site sequencing to speed gene discovery, gene structure analysis, mutation characterization, analysis of vector constructs, etc. The capacity for genomics efforts using genotyping and LOH analyses will be greatly expanded by the requested equipment. Frequent quality control, assessments will be used to validate the accuracy, quality and throughput of all Core services. The Core will provide educational opportunities to the Mount Sinai community through minicourses, presentations and workshops and will promulgate investigator awareness of the availability and features of Core services through creation of a Website, campus-wide Email announcements and a biannual newsletter. The Core will continuously evaluate and implement new protocols, upgrades and technology to provide optimal resources for NIH-supported research. Importantly, equitable, cost-effective and responsive Core services will be promoted through an Institutional Advisory Committee. This multidisciplinary committee will provide oversight and coordination of Core services, will review costs and income regularly and annually adjust prices to achieve the lowest possible costs to investigators. They will also identify and recommend novel strategies, technologies, instrumentation, and resources to further facilitate and foster cutting-edge research. In summary, the requested equipment will fit synergistically with existing resources and our Dean's major genomics/bioinformatics initiatives to markedly enhance research productivity.